Role Found for Natural Body Opioids in Reproduction and Resistance to Infection

NATIONAL INSTITUTES OF HEALTH, National Institute on Drug AbuseFOR IMMEDIATE RELEASE, Tuesday, Apr. 22, 1997, Mona W. Brown, Sheryl Massaro

Scientists have discovered that the body's natural opioid system is far more important and has broader effects than ever thought. In addition to being essential to responses to pain and the euphoria from drugs such as morphine, codeine, and heroin, the mu opioid receptor, the cellular target of these drugs, also appears to be involved in regulating the immune and reproductive systems.

Researchers at the Indiana University School of Medicine have shown that, in addition to failing to respond to narcotic drugs, like morphine, mice missing the gene for the mu opioid receptor also show reduced sexual and reproductive function and altered immune systems.

Dr. Lei Yu and his colleagues showed that when the functioning of the mu opioid receptor is disabled by a technique called "knocking out" the gene responsible for its production, mice not only fail to respond to the pain-relieving properties of morphine, but their sexual behavior, their reproductive functioning, and their immune systems are also modified. Mice lacking mu opioid receptors experienced increased production of blood progenitor cells, including white blood cells which defend the body against infection, in their bone marrow and spleen. In addition, male mice lacking mu opioid receptors engaged in less mating activity; had fewer, less active sperm; and fathered smaller litters than did male mice with intact mu opioid receptors.

It has been known since the 1970s that the body has a natural opioid system that acts much in the same way as opiate drugs like heroin and morphine. Not only are there receptors throughout the body that respond to opiate substances, but the body produces natural opioids that are released during strenuous exercise and in response to stress or pain. These natural substances are involved in the body's control of pain reactions and play a role in many other behaviors, like the experience of pleasure.

Although the effects of the mu opioid receptor on perceiving pain or pleasure may seem unrelated to the immune and reproductive systems, Dr. Yu suggests that, "These results indicate that the mu opioid receptor is involved in a range of diverse biological processes."

Dr. Alan I. Leshner, Director of the National Institute on Drug Abuse, which supported this study, said, "These observations in the mouse model track very well with anecdotal accounts that humans using heroin and morphine experience both reduced immune function and reduced sex drive. Not only do opiates affect mood states and produce addiction, but it also appears that their effects on natural opioid receptors lead to changes in their capacities to reproduce and to resist infection and disease. The findings emphasize the very broad implications of narcotic drug use on both the health of an individual and the public."

Dr. Leshner added, "This study builds on Dr. Yu's earlier work, where he and his colleagues first broke the genetic code for the mu opioid receptor. They now have demonstrated its importance in many different biological arenas. Understanding both the structure and, now, the broader range of functions of this receptor will aid tremendously in our efforts to develop medications to address the problem of opiate use and addiction and their resulting health consequences."

The study was published in the April 21, 1997, issue of the Journal of Experimental Medicine.

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